Cloning and regulation of an endothelial cell protein C/activated protein C receptor

Abstract

Human protein C and activated protein C were shown to bind to endothelium specifically, selectively and saturably (Kd=30 nM, 7000 sites per cell) in a Ca 2+ dependent fashion. Expression cloning revealed a 1.3 kb CDNA that coded for a novel type I transmembrane glycoprotein capable of binding protein C. This protein appears to be a member of the CD1/MHC superfamily. Like thrombomodulin, the receptor involved in protein C activation, the endothelial cell protein C receptor (EPCR) function and message are both down regulated by exposure of endothelium to TNF. Identification of EPCR as a member of the CD1/MHC superfamily provides insights into the role of protein C in regulating the inflammatory response, and determination of methods for pharmaceutical use in manipulating the inflammatory response.

We claim:  
     
       1. An isolated antibody or antibody fragment immunoreactive with a human endothelial cell protein C/activated protein C receptor but not reactive with CCD41 or CD1d. 
     
     
       2. The antibody of  claim 1  wherein the receptor is encoded by the nucleotide sequence of SEQ ID NO:1 and degenerative sequences thereof. 
     
     
       3. The antibody of  claim 1  wherein the receptor has the amino acid sequence of SEQ ID NO:2. 
     
     
       4. The antibody of  claim 1  wherein the isolated antibody is an antibody fragment. 
     
     
       5. The antibody of  claim 1  wherein the complementarily-determining hypervariable regions of the antibody binds only to an epitope of the endothelial cell protein C/activated protein C receptor which is unique to the isolated endothelial cell protein C/activated protein C receptor. 
     
     
       6. The antibody of  claim 1  wherein the antibody is a labeled antibody.